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Adrenergic Receptor Agonists• Termed sympathomimetic drugs• Divided into three groups• Direct-acting agonists

– Catecholamines– Noncatecholamines

• Indirect-acting agonists • Mixed acting agonists

59-291 Section 2, Lecture 4

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Catecholamines• Naturally occurring:

– NE: endogenous sympathetic neurotransmitter– EP: The principle hormone of adrenal medulla– Dopamine: Precursor to EP and NE

• Synthetic: Isoproterenol, dobutamine• Structure: catechol moiety, ethylamine side chain• Inactivation: COMT, MAO; found in the gut, liver

and other tissues• Low oral bioavailability, short plasma half-lives • Must be administered parenterally for systemic

actions; Anaphylactic shock

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Mechanisms and Effects• Cathecolamines differ in their affinities and

specificities for receptors• Size of alkyl substitution on the amine

nitrogen determines the relative affinity for and receptors

• Larger alkyl group, higher affinity for receptors; Isoproterenol

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NE: Constricts all blood vesselsEP: Constricts some blood vessels but dilates the others Dopamine: stimulates release of NE from sympathetic nerves(Direct and indirect agonist)

Ethylamine

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Drug Pharmacologic Effect (and Receptor)Direct-acting catecholamines

Dobutamine Cardiac stimulation (β1) and vasodilation (β2)

Dopamine* Renal vasodilation (D1), cardiac stimulation (β1), and increased blood pressure (β1 and α1)

Epinephrine Vasoconstriction and increased blood pressure (α1), cardiac stimulation (β1), and bronchodilation (β2)

Isoproterenol Cardiac stimulation (β1) and bronchodilation (β2)

Norepinephrine Vasoconstriction and increased blood pressure (α1)

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Drug Clinical UseDirect-acting catecholamines

Dobutamine Cardiogenic shock, acute heart failure, and cardiac stimulation during heart surgery

Dopamine* Cardiogenic shock, septic shock, heart failure, and adjunct to fluid administration in hypovolemic shock

Epinephrine Anaphylactic shock, cardiac arrest, ventricular fibrillation, reduction in bleeding during surgery, and prolongation of the action of local anesthetics

Isoproterenol Asthma, refractory atrioventricular block, and refractory bradycardia

Norepinephrine Hypotension and shock

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Sys, Dias., MeanArt. P

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Adverse effects: -excessive vasoconstriction leading to ischemia

-reduces blood flow to vital organs such as kidneys; cause excessive cardiac stimulation leading to myocardial ischemia or arrythmias

--adrenergic agonists: hyperglycemia undesirable in diabetics

Indirect-ActingAmphetamine- induces the release of NECocaine-prevents reuptake of NE

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Mixed-Acting: the name says it all! Direct and Indirect acting adrenergic agonists

activate both α and receptors Ephedrine and Pseudoephedrine vasoconstriction via 1 receptors; useful as nasal decongestants; via bronchodilate

Adverse effects: tachycardia, hypertension, urinary retention

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Practice Questions• Which of the following drugs does

stimulate mainly receptors– NE– EP– Isoproterenol– Dopamine

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• Which of the following catecolamines may cause reflex bradycardia due to stimulation of 1 receptors?– NE– EP– Dopamine – Isoproterenol

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• What is the treatment of choice for anaphylactic shock– NE– EP– Isoproterenol– Dobutamine